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Article history: Assessment of a pediatric breast lesion always starts with clinical evaluation. When imaging of a pediatric
Received 16 October 2014 breast is indicated, ultrasound is the mainstay. The vast majority of pediatric breast complaints are of
Received in revised form 10 April 2015 benign etiology, therefore the diagnostic/management approach emphasizes “first do no harm”. Correla-
Accepted 11 April 2015
tion with age and clinical history helps to direct diagnosis. It is essential to be familiar with the imaging
appearance of the normal developing breast at various Tanner stages, in order to diagnose physiologic
Keywords:
breast findings and to minimize unnecessary biopsies in young breasts vulnerable to injury. Normal
Pediatric breast lesions
anatomic structures, developmental conditions, benign neoplastic and non-neoplastic lesions are com-
Breast evaluation in children and
adolescents
mon causes of breast complaints in children. Uncommon benign masses and rarely, secondary more than
Developing breast primary malignancies may present in a pediatric breast. Chest wall masses such as Ewing’s sarcoma or
Breast cancer in children rhabdomyosarcoma occur in children and may involve the breast via contiguous growth or locoregional
Breast ultrasound metastasis. In addition, special attention should be given to any breast lesion in a child with risk factors
predisposing to breast cancer, such as known extramammary malignancy, genetic mutations, prior man-
tle irradiation, or strong family history of breast cancer, which usually requires biopsy to exclude the
possibility of malignancy.
Conclusion: The developing breast is vulnerable to injury, and because breast malignancy is uncommon
in children, diagnostic and management approach emphasizes “first do no harm”. Understanding normal
breast development and the spectrum of common and uncommon pediatric breast lesions are key to the
correct diagnosis.
© 2015 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejrad.2015.04.011
0720-048X/© 2015 Elsevier Ireland Ltd. All rights reserved.
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A 2–3 cm probably benign mass on ultrasound in a child with- 3. Normal breast development
out atypical features or rapid enlargement is rarely malignant and
is safe to follow, as has been shown in multiple studies. Biopsy The breast begins normal development during the 5–6th week
should be considered however if the mass is larger than 4–5 cm of fetal gestation [4], with ectodermal cells invaginating into the
or undergoing rapid enlargement, to exclude the possibility of a deeper mesenchyme to form the mammary ridges or milk lines,
phyllodes tumor. Other rare benign masses in the pediatric breast which extend symmetrically along the anterior torso from the axil-
include hamartoma, intraductal papilloma, juvenile papillomatosis lae to the groin (Fig. 1). Over time, there is normal involution
(a marker for familial breast cancer), and fibrous nodule. Malignant of the milk lines except at the level of the 4th intercostal space,
lesions in the pediatric breast are exceedingly rare, more com- where normal breast buds form. If normal involution is incom-
monly metastatic disease to the breast and occasionally primary plete, ectopic or accessory nipples and/or breast tissue may form
breast malignancy. Phyllodes tumor is the most common primary anywhere along these milk lines. At the 4th intercostal space, the
breast malignancy in children. Invasive ductal carcinoma is rare in primary breast buds (invaginated epidermal cells) evolve into sec-
children, of which the secretory subtype is the most common. In ondary buds and further branch into lactiferous ducts within the
young people with risk factors predisposing to breast cancer, such breast parenchyma. Overlying the breast bud at the skin surface, a
as strong family history of breast cancer, known extramammary small depression or mammary pit forms, which further evolves into
malignancy, genetic mutations, or prior mantle irradiation, biopsy the nipple–areolar complex (Fig. 2). Prior to puberty, the breast is
is often required to exclude malignancy regardless of the imaging composed of epithelium lined lactiferous ducts supported by stro-
appearance of the breast lesion. mal connective tissue [5]. Enlargement of these ducts are a common
In this article, we will review embryology and development cause of self-limited bilateral palpable subareolar nodules in both
of the breast, discuss the appropriate imaging and management male and female infants in the first 6–12 months of life due to
approach of pediatric breast complaints, and explore the spectrum maternal hormonal influence [6].
of common and uncommon pediatric breast lesions. With the onset of puberty, the breast undergoes further matura-
tion. The term thelarche refers to the onset of normal pubertal phase
of breast development in females, with estrogen stimulating ductal
2. Imaging approach to the pediatric breast growth and progesterone promoting lobular and alveolar differen-
tiation, completing the terminal duct lobular unit. The normal age of
Because pediatric breast cancer is so rare, diagnostic imaging onset of thelarche in the U.S. ranges between 9 and 10 years of age,
emphasizes “First Do No Harm”. Evaluation of pediatric breast with the average onset of thelarche in African American girls gener-
complaints always begins with clinical assessment, which then ally being earlier compared to that in Caucasian girls [7]. Premature
determines the need for imaging. Ultrasound remains the primary thelarche therefore, is defined as early onset of breast development
and often the only necessary modality for the evaluation of breast in prepubertal girls, typically before age 7–8. Thelarche after 12
complaints in the pediatric population, given its high sensitivity years of age is considered delayed [8].
for detection of lesions in younger denser breasts [3] and the lack Idiopathic premature thelarche generally occurs in younger
of ionizing radiation. In contrast, the utility of mammography is children between ages 1–3 [6], and is unusual after age 4 [9]. Idio-
limited in the pediatric population, both due to low diagnostic sen- pathic premature thelarche is benign and generally self-limited.
sitivity in young and dense breasts, and radiation risks associated This can however mimic a mass when unilateral, and thus fre-
with mammography in this age group. MRI and other cross sec- quently comes to clinical attention. The role of ultrasound is to
tional imaging modalities are generally reserved for assessment of confirm the presence of normal developing breast tissue or the-
disease extent, for assessment of deep chest wall lesions or vascular larche (whether premature or appropriate), in the absence of
anomalies, or occasionally for correlation with ultrasound findings. a discrete mass. Clinical reassurance and followup usually suf-
Breast Imaging Reporting and Data System lexicon (currently fice for idiopathic isolated premature thelarche, but occasionally
5th edition) is the gold standard for describing and stratifying short term imaging followup may be appropriate. Other possible
breast lesions into categories which correlate with likelihood of
malignancy by imaging appearance (Table 1). Although this is used
both in adults and in children, because it is based on the likelihood
of malignancy, which is exceedingly low in children [2], its utility
may be limited in this setting. For example, the vast majority of
pediatric breast lesions are benign and will be categorized BIRADS
2 or 3, emphasizing appropriate conservative management to “First
Do No Harm”. Highly suspicious lesions or lesions in high risk pedi-
atric patients may warrant biopsy and are categorized BIRADS 4 or
above, but are few and far in between.
Table 1
BI-RADS assessment categories and likelihood of cancer. American College of Radi-
ology BI-RADS© Atlas 2013.
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Fig. 2. Breast development – Ectodermal cells invaginate to form the primary breast bud, which branches into secondary buds, and then subsequently branch and elongate
further to form the lactiferous ducts. Externally a mammary pit or indentation is formed in the skin, which evolves into the nipple areolar complex (Susanne Loomis, MS,
FBCA of MGH REMS Media Service).
Fig. 3. Clinical tanner stages of normal breast development (Susanne Loomis, MS, FBCA of MGH REMS Media Service).
factors linked to isolated premature thelarche include high body ductal structures. Tanner stage 3 and 4 breast tissues demonstrate
mass index [10] and herbal intake [11]. appearance of further expansion of the hyperechoic fibroglandular
Premature thelarche can also occur in conjunction with preco- elements, with the central retroareolar hypoechoic regions evolv-
cious puberty. It is important to ensure that there are no other signs ing into more branching and eventually nodular configurations. The
of sexual maturation associated with premature thelarche such Tanner stage 5 breast shows the appearance of mature echogenic
as development of axillary and pubic hair, in which case further breast tissue without central hypoechogenicity, as seen in the adult
imaging and laboratory workup would be indicated to exclude hor- breast.
monally active adrenal or gonadal neoplasms as potential causes for
precocious puberty. 4. Common causes of pediatric breast complaints
There are five Tanner stages of normal pubertal breast devel-
opment based on the clinical appearance of the developing breast 4.1. Normal anatomic structures
(Fig. 3). Ultrasound appearances of the breast at various Tan-
ner stages have been well described and familiarity with these 4.1.1. Normal lymph node
appearances is critical for the radiologist performing pediatric Normal lymph nodes reside in the axilla, axillary tail, and
breast evaluation [6,12]. Sonographically, the Tanner stage 1 breast breast parenchyma, and can become clinically palpable. Intra-
appears as mildly heterogeneous retroareolar tissue. The Tanner mammary lymph nodes are most commonly found in the upper
stage 2 breast appears as a hyperechoic nodule with central lin- outer quadrants of the breasts. A prominent node in an otherwise
ear or stellate areas of hypoechogenicity which represent evolving healthy young patient is most commonly due to reactive nodal
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Fig. 4. 17 year old girl with prominence of left axillary tail following intended weight
loss. Ultrasound was performed of the left axilla in the area of clinical concern,
demonstrating a normal lymph node with hypoechoic cortex of normal thickness
(<3 mm) and hyperechoic central fatty hilus.
Fig. 6. 3 year old boy with rhabdomyosarcoma and normal asymmetric breast buds
(arrows) on post treatment surveillance CT.
hypertrophy, or occasionally from relative loss of soft tissue sur-
rounding a lymph node (for example, weight loss), causing it
to become clinically more prominent. Ultrasound is definitive in
incidentally noted on CT performed for another indication can occa-
the identification of a normal lymph node, which appears as a
sionally lead to concern for a breast mass (Fig. 6). It is important to
bean shaped or oval structure with hypoechoic sub-3-mm cor-
be familiar with the appearances of normal breast buds at differ-
tex and echogenic central fatty hilus (Fig. 4). Hilar vascular flow
ent stages of evolution in order to avoid unnecessary biopsy which
is helpful for diagnosis at real time sonography. A normal lymph
places the young patient at risk for iatrogenic hypomastia or amas-
node is a benign finding and clinical followup suffices. The typical
tia. Once benign breast bud asymmetry is confirmed, clinical follow
appearance of reactive nodal hypertrophy is mild diffuse cortical
up is appropriate. Further imaging is usually not indicated.
thickening. Common causes of reactive axillary lymphadenopathy
include viral illness and vaccination, both frequently encountered
in children. Sonographic evidence of abnormal findings such as 4.1.3. Osseous structures
eccentric cortical thickening or displacement of central fatty hilum Osseous structures can occasionally account for areas of clinical
suggest possible malignant nodal involvement and warrant tissue concern in the region of the breast, particularly in thin patients or
sampling. patients with rib and chest wall deformities such as pectus exca-
vatum, pectus carinatum, or in the setting of Poland syndrome
4.1.2. Normal breast bud (Fig. 7). Clinical exam usually reveals a fixed firm mass contigu-
Asymmetric normal breast development is a common cause of ous to the remainder of bony structures. If uncertainty remains
unilateral subareolar mass in children. Asymmetry between the after physical examination, chest radiography could obtained to
breast buds is common, with differences of up to 2 years in the assess for osseous abnormalities, and ultrasound can be performed
phase of development between the breasts considered to be within to evaluate the focal area of concern and to exclude a mass or other
the normal spectrum [12]. Ultrasound may be performed to con- abnormality.
firm the presence of normal breast buds and the absence of other Poland syndrome is an autosomal recessive disorder, marked
abnormalities (Fig. 5). Early development of the breast bud is called by unilateral partial or complete absence of the pectoralis mus-
premature thelarche, which is most common in children under cle, associated with breast hypoplasia or aplasia, rib and chest wall
age 3. Benign isolated premature thelarche usually regresses on deformities, as well as ipsilateral limb abnormalities (Fig. 8). It is
its own. Imaging findings of normal or premature development of important to recognize that breast cancer occurs in the hypoplas-
breast buds are similar. Ultrasound shows subareolar hypoechoic tic breast in a patient with Poland syndrome, and that routine
stellate breast tissue without associated mass (Fig. 5). Although mammographic screening is indicated in these patients in adult-
CT is not indicated in this setting, normal breast asymmetry hood [13–15]. Of the reported cases of breast cancer in the setting
Fig. 5. 5 year old boy with mobile subareolar right breast mass discovered by mother. Ultrasound demonstrates asymmetric but normal breast buds, right larger than left.
There is no mass in the subareolar right breast in the area of clinical concern.
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Fig. 7. 17 year old girl with Poland syndrome notes a firm lump along the right sternal border. (a) Ultrasound shows a hypoechoic shadowing structure at the right
costomanubrial junction, felt to be related to the thoracic skeleton. (b) Chest radiograph demonstrates near complete absence of the right breast shadow consistent with
Poland syndrome and confirms the source of clinical concern to be a normal anterior rib.
4.2.2. Gynecomastia
Gynecomastia is excess breast tissue development in males,
which can present clinically as subareolar tenderness and or a
Fig. 8. MLO mammographic views demonstrate absence of the left pectoralis major palpable mass. It can be unilateral or bilateral, and it has been
muscle and left breast hypoplasia in a patient with Poland syndrome. reported to be familial. The cause of gynecomastia is unknown but
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4.3.1. Cyst
Cysts (within the spectrum of fibrocystic change) in the breast
are most common in women between ages 35–50, but they can
also occur in children and adolescents [8]. Cysts may arise from
dilatation of the lobular acini possibly due to imbalance of fluid
secretion and resorption, or due to obstruction of the duct lead-
ing to the lobule [20]. Cysts are more commonly solitary than
multiple in children [6], and can often present as a palpable abnor-
mality in the breast, occasionally associated with tenderness when
associated with inflammation or infection. Most cysts are treated
conservatively, with some rarely requiring antibiotic therapy or
drainage if infection is suspected. On ultrasound, if a simple cyst
is demonstrated as an anechoic structure with imperceptible wall
and posterior acoustic enhancement (Fig. 11), benign diagnosis
Fig. 9. 20 year old woman with enlarging left axillary lump. Ultrasound of the left
axilla demonstrates focal area of normal fibroglandular tissue. is confirmed and no further imaging or intervention is indicated.
However if the cyst appears to be thick walled and or contains
internal echoes, diagnostic considerations should include a com-
plicated cyst, an abscess, a galactocele, or focal duct ectasia in the
appropriate clinical contexts.
4.3.2. Hematoma
A hematoma is an area of localized hemorrhage. In children
and adolescents, hematomas in the breast are often seen in con-
junction with sports injuries, iatrogenic trauma, or activity related
injuries such as bike handle bar injury. A clear history of trauma
and careful physical exam for signs of superficial bruising over the
breast help confirm the diagnosis. On ultrasound, a hematoma can
appear as a solid or complex cystic mass. Sonographic appearance
of a hematoma varies depending on the age of the blood products.
More acutely, a hematoma appears hyperechoic. It becomes pro-
Fig. 10. 17 year old boy with right subareolar tender swelling. Ultrasound of the gressively more anechoic as it regresses over time [21]. Because
right breast shows prominent fibroglandular tissue directly deep to the nipple, blood products can incite reactive changes, a hematoma can
consistent with gynecomastia.
have irregular or even spiculated margins, mimicking malignancy
(Fig. 12). This highlights the importance of a thorough clinical his-
tory and a careful clinical exam, which can obviate unnecessary
biopsy. When the diagnosis of hematoma is established, short-term
thought to be related to relative elevation of circulating estrogen follow up by ultrasound is recommended to ensure resolution.
with respect to testosterone. In adults, gynecomastia may be idio-
pathic or has been associated with chronic liver disease, excess
4.3.3. Abscess
body fat, marijuana or exogenous steroid intake, or medications
Although more commonly encountered in lactating women,
such as cimetidine, digitalis, and tricyclic antidepressants. In chil-
mastitis and abscess can occur in childhood. Mastitis occurs most
dren, gynecomastia is often physiologic and is most common in
frequently in infants (age < 2 months; i.e. mastitis neonatorum)
neonates and adolescents. Up to 90% of neonates have transient
and later childhood (age 8–17), and is thought to be related to
breast hypertrophy due to maternal hormonal influence [3], and
skin infection and or ductal obstruction [22]. Typically, suppura-
clinical reassurance usually suffices. During puberty, gynecomas-
tive mastitis presents with edema and erythema, occasionally with
tia is present in up to two thirds of 10–13 year old boys [19],
fever and leukocytosis. Ongoing mastitis can lead to the devel-
which usually subsides within two years, and clinical followup is
opment of phlegmon and abscess. The most common pathogen
appropriate. Ultrasound is the modality of choice in children, and
is Staphylococcus aureus, followed by Streptococcus and less com-
typically demonstrates increased retroareolar fibroglandular tissue
monly Enterococcus species [22]. Ultrasound should be performed
similar to the appearance of the early developing female breast
(Fig. 10), consistent with gynecomastia. In adult males, mammo-
grams are diagnostic for gynecomastia, most commonly showing
retroareolar flame shaped breast tissue.
If however gynecomastia presents in prepubertal boys, other
causes should be considered. Estrogen producing tumors such
as testicular Leydig cell tumor, adrenal cortical tumor, or
gonadotropin secreting tumors such as hepatoblastoma, fibro-
lamellar hepatocellular carcinoma, or choriocarcionoma can
cause gynecomastia. Other causes include prolactinoma, testi-
cular feminization, Klinefelter syndrome, neurofibromatosis type 1,
medications, and herbal remedies [3,6]. In prepubertal boys, clin-
ical exam suggestive of gynecomastia should prompt correlation
Fig. 11. 17 year old girl presents with persistent “nodule” in the upper outer right
with clinical history and further imaging and laboratory exams to breast. Ultrasound shows a nonvascular circumscribed thin-walled anechoic struc-
exclude underlying disease. ture with posterior acoustic enhancement, consistent with a simple cyst.
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Fig. 14. 15 year old Somali refugee who is 1 month postpartum and breast feed-
ing, presents with right breast lump. Ultrasound shows a circumscribed oval cystic
mass of mixed internal echogenicity, in the setting of breast feeding, suggestive of
fatty milky contents. This was aspirated for symptom relief, yielding milky fluid,
Fig. 12. 15 year old girl with known sports related trauma to the chest presents with consistent with a galactocele.
an area of palpable concern. Targeted ultrasound to this site of trauma demonstrates
a non-vascular irregular anti-parallel predominantly hypoechoic mass, with mild
adjacent soft tissue induration, consistent with hematoma. This resolved completely contents (Fig. 14). Occasionally, a fat-fluid level may be present,
on the follow up ultrasound six weeks later. which is visualized on ultrasound as well as on mammography.
This is diagnostic of a galactocele. Clinical history and imaging
in patients with clinical symptoms of infection to exclude presence appearance often suggestive the diagnosis. Aspiration of milky fluid
of a drainable fluid collection. The ultrasound typically shows skin confirms the diagnosis of a galactocele in the setting of complex and
thickening and hyperechoic indurated breast tissue associated with or atypical imaging appearance, and provides symptomatic relief.
hyperemia (mastitis). Occasionally, a hypoechoic complex mass
(phlegmon or developing abscess), or an organized thick walled 4.4. Benign masses
complex fluid collection is present (frank abscess) (Fig. 13). Treat-
ment includes antibiotic therapy and prompt ultrasound guided 4.4.1. Fibroadenoma
drainage, which helps facilitate healing and provides material for Fibroadenomas are benign fibroepithelial tumors and are the
culture and sensitivity testing to further tailor therapy. most common solid breast masses found in adolescent girls [23].
Because fibroadenomas arise from proliferation of specialized con-
4.3.4. Galactocele nective tissue stroma surrounding breast lobules, they do not
Galactoceles are retention cysts of milky fluid in the breast, usually occur in the male breast where lobules are typically
most commonly seen in pregnant, lactating, or early post lacta- absent, although male fibroadenomas have been reported in rare
tional women, but can occasionally present in children and young cases. Fibroadenomas are estrogen sensitive tumors and may grow
infants with or without endocrinopathy [3,6]. A galactocele likely rapidly during puberty and pregnancy. The classic clinical presen-
results from occlusion of a lactiferous duct, therefore histologi- tation of a typical fibroadenoma is a nontender palpable mobile
cally represents a cyst with walls lined by cuboidal to columnar rubbery mass usually 2–3 cm in size [24] (Fig. 15). At ultrasound,
epithelium [31]. Galactoceles can persist up to several years post fibroadenomas are usually parallel, circumscribed, oval hypoechoic
lactation. Sonographically, a galactocele appears as a complex cys- masses, but may exhibit macrolobulations and become irregular in
tic mass with variable internal echotexture depending on the shape as they grow into larger masses [25]. A pseudocapsule may
relative milk (hyperechoic) versus water (hypoechoic/anechoic) be seen in certain cases [25] (Fig. 15). The internal echotexture
Fig. 13. 14 year old girl with left areolar swelling, redness, pain, and fever for 1 week. Targeted ultrasound to the periareolar left breast demonstrates skin thickening and an
underlying complex fluid collection, consistent with abscess (a, b). The abscess was drained to completion under ultrasound guidance (c), yielding 3–4 cc of purulent fluid.
This was sent for culture and grew Staphylococcus Aureus.
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Fig. 16. 15 year old lacrosse player presents with left breast lump. Ultrasound demonstrates a parallel non-vascular hypoechoic mass with slightly irregular margins anteriorly
and posterior acoustic enhancement, prompting biopsy showing a fibroadenoma (a, b). A year later, the patient returns feeling “the lump is a lot bigger”. Ultrasound shows
interval enlargement of the same mass, with surgical excisional biopsy recommended, yielding final pathology of fibroadenoma.
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Fig. 17. 13 year old girl with rapidly enlarging breast mass. Ultrasound shows a large circumscribed mass exceeding the span of the linear ultrasound probe, estimated up
to 10 cm in the largest dimension, with relatively homogeneous internal echotexture. This was surgically excised with pathology demonstrating juvenile fibroadenoma.
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Fig. 19. 16 year old boy with serosanguinous left nipple discharge for one month. Ultrasound of the subareolar left breast shows an oval iso- to hyperechoic intraductal
mass outlined by fluid within a dilated duct (b). Ultrasound needle localized surgical excision was performed. Whole slide pathology image (a) shows histologic–radiologic
correlation of the intraductal mass. A solitary papilloma is present within an epithelium-lined lactiferous duct (c). Higher power microscopy shows a papillary structure
consisting of a fibrovascular core (d) (black arrows) with connective tissues and small blood vessels, lined by benign epithelium (black arrowhead).
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Fig. 22. 16 year old girl with cutaneous T cell lymphoma involving the right breast, initially presenting as non healing rash. CT shows an irregular infiltrative mass along the
superficial aspect of the right breast (a), which is FDG avid on PET CT (b), and consistent with subcutaneous panniculitis-like cutaneous T cell at biopsy.
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Fig. 23. 13 year old girl notes a subcutaneous mass in the right breast, present for 6 weeks. Ultrasound shows a large solid and cystic complex mass with heterogeneous
internal echotexture and interspersed linear anechoic clefts (a, arrows). Biopsy was the mass was performed, with whole pathology slide (b) demonstrating an intermediate
grade phyllodes tumor with overall variegated architecture consisting of fronds, classic for phyllodes tumor. Spaces between fronds correlate well with the sonographic
feature of clefts often seen in these tumors.
enlarging breast mass in children (more specific features of a phyl- cancer later in life. This population has a cumulative incidence
lodes tumor). Surgical excision with wide margins is required for of breast cancer of 12–20% by about age 40, comparable to that
all phyllodes tumors. in the BRCA (breast cancer susceptibility) gene mutation carriers
Low grade phyllodes tumors are generally associated with lower (10–19%), whereas in the general population, women of the same
rate of recurrence [48]. In children, recurrence rate of phyllodes age group have a cumulative incidence of breast cancer of 1% [53].
tumor is even lower, estimated at approximately 10% [49]. Local Young women at the greatest risk are those treated with therapeu-
recurrence does not alter prognosis. Histologic features of phyl- tic radiation between ages 10–16, with the majority of the tumors
lodes tumors include increased stromal cellularity, cellular atypia, developing in the radiation field [3]. The risk of breast cancer
stromal overgrowth, and presence of sarcomatous elements, the increases with years post irradiation, therefore routine screening
latter of which used to define the malignant type [48]. Based on is important. Annual screening mammogram with adjunctive MRI
these histologic criteria, phyllodes tumors are generally classi- screening are generally recommended in young women at least 25
fied into low-grade, intermediate-grade, or high-grade (malignant) years of age, 8–10 years following completion of radiation therapy
tumors (Fig. 23). Classification into benign and malignant lesions is as per the American College of Radiology guidelines [54]. The imag-
occasionally used. Phyllodes tumors exhibit an overall variegated ing appearance of breast cancer arising after therapeutic irradiation
architecture (Fig. 23b), and consist of fronds (cellular stromal tissue is not different from other primary breast cancers.
lined by epithelium), allowing for cystic or cleft like spaces between
abutting fronds on ultrasound (Fig. 23a). 5.2.7. Hereditary breast cancer/Cowden syndrome
Approximately 10% breast cancers are hereditary. Known asso-
5.2.5. Invasive secretory carcinoma ciated factors include not only the BRCA1 and BRCA2 mutations,
Primary breast carcinomas are exceedingly rare in the pediatric but also rare germline mutations such as TP53 mutations in Li-
population. Primary breast cancer incidence is noted to be approxi- Fraumeni syndrome, STK11 mutations in Peutz-Jeghers syndrome,
mately 0.1 case per million in females younger than 20 years of age and PTEN mutations in Cowden syndrome [55]. New mutations
[2]. Boys are even less affected (Figs. 24 and 25). continue to emerge with further advances in genomic technology.
The most common subtype of invasive breast cancer in children The hallmark of hereditary breast cancer is early onset of disease,
is invasive secretory carcinoma, which carries a more favorable highlighting the importance of early screening.
prognosis as compared to the less common subtypes of breast can- Cowden syndrome is also known as multiple hamartoma
cer seen in children (invasive ductal, invasive lobular, medullary, syndrome. Together with Bannayan-Riley-Ruvalcaba syndrome,
inflammatory, and anaplastic carcinomas) [5,50,51]. Secretory car- Cowden syndrome belongs to the spectrum of hamartomatous
cinomas are small circumscribed masses (usually < 3 cm) that overgrowth syndromes associated with germ line mutations in the
present as painless palpable masses (Fig. 24). On ultrasound, tumor suppressor PTEN gene which is located on 10q23.3, with an
they typically appear as circumscribed or partially microlobu- autosomal dominant inheritance. However, not all patients with
lated hypoechoic masses with heterogeneous internal echotexture clinical diagnosis of Cowden syndrome have an identifiable PTEN
[52] (Fig. 24). Secretory carcinoma contains bubbles of secretory mutation [56]. PTEN mutation carriers are at significantly increased
components or cytoplasmic vacuoles on histology, which are char- risks for breast, thyroid, endometrial, and renal cell carcinomas
acteristically positive by PAS stain (Fig. 24b). Treatment is surgical (Fig. 26). Cowden syndrome patients carry a cumulative breast can-
excision, sentinel node biopsy, with or without systemic adjuvant cer risk of 77% by age 70, and 75% of these patients have breast
therapy depending on the disease extent. lesions of some kind (Fig. 26) [57]. Given the markedly elevated
risks for breast cancer, guidelines have proposed commencing clin-
5.2.6. Post radiation breast cancer ical breast exam and screening breast ultrasound at age 25, and
Children who receive high dose mantle irradiation for Hodgkin’s starting screening mammogram and MRI at age 30 or 5 years before
disease are at significantly increased risk for developing breast earliest known breast cancer in the family [57].
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Fig. 24. 8 year old boy with family history of breast cancer presents with a painless right periareolar breast lump for 1.5 years with recent increase in size. Ultrasound shows
a circumscribed oval predominantly hypoechoic mass (a) which corresponds well with whole slide pathology mount (b). Surgical excisional biopsy shows invasive secretory
carcinoma, solid variant, and in situ secretory carcinoma. Mastectomy was ultimately performed for positive surgical margin at the initial resection. Sentinel node biopsy was
negative. Higher power microscopy of the mass shows jagged edges of invasive tumor cells along the periphery (c. arrows). PAS stain is positive, highlighting the presence
of intracytoplasmic vacuoles (arrows).
6. Management algorithm
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14 Y. Gao et al. / European Journal of Radiology xxx (2015) xxx–xxx
Fig. 26. 15 year old girl with Cowden syndrome presents with innumerable palpable bilateral circumscribed homogeneous breast masses with a representative example
displayed here on ultrasound (a). The patient had already undergone prior bilateral breast biopsies demonstrating benign histologies including a complex sclerosing lesion
with PASH (b), therefore surveillance of the remaining masses rather than biopsy was recommended. This patient also has a history of papillary thyroid cancer requiring
thyroidectomy, and has over 50 polyps throughout the gastrointestinal tract in the esophagus, stomach, and colon.
Fig. 27. How to approach breast lesions in children and adolescents – a diagnostic and management algorithm.
occurs. Larger than 5 cm masses meeting criteria as probably benign estrogen secreting tumors in rare cases. Children with nipple dis-
cannot be readily differentiated from phyllodes tumors, and there- charge should be examined and ultrasound may rarely show an
fore, biopsy is indicated. Mass lesions with malignant features on intraductal papilloma or juvenile papillomatosis, both of which
ultrasound (indistinct/angular/microlobulated/spiculated margin, require surgical resection, the latter of which is associated with
irregular shape, and anti-parallel orientation) should be biopsied. elevated risk of developing breast cancer later in life.
Initial discovery of any breast mass, regardless of appearance in
patients with known extramammary malignancy, prior mantle 7. Conclusion
radiation, genetic mutations or syndromes, warrants sampling.
Other cross sectional imaging modalities such as CT, MR, FDG-PET Breast malignancy is exceedingly rare in children. Diagnostic
are often helpful in defining disease extent. and management approach of the pediatric breast is therefore
Gynecomastia is most commonly physiologic in neonates and appropriately conservative. It is important to understand that
teenage boys. A clinical and laboratory workup should be consid- the spectrum of pediatric breast disease differs from that of the
ered however, in prepubertal boys with gynecomastia to exclude adult breast. Knowledge of common and uncommon benign and
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